Tamoxifen induces toxicity, causes autophagy, and partially reverses dexamethasone resistance in Jurkat T cells

Autor: Andrómeda Liñán-Rico, Luis Donis-Maturano, Arturo Hernández-Cruz, Liliana Torres-López, Oxana Dobrovinskaya, Paola Maycotte, Ivan Delgado-Enciso, Clemente Vásquez-Jiménez, Carmen Meza-Robles, Liliana Liñan-Rico
Rok vydání: 2019
Předmět:
CD4-Positive T-Lymphocytes
0301 basic medicine
Antineoplastic Agents
Hormonal
Cell Survival
Primary Cell Culture
Immunology
ATG5
Estrogen receptor
Biology
Lymphocyte Activation
Jurkat cells
Dexamethasone
Autophagy-Related Protein 5
Receptors
G-Protein-Coupled
Jurkat Cells
03 medical and health sciences
0302 clinical medicine
stomatognathic system
Cell Line
Tumor
Autophagy
Estrogen Receptor beta
Humans
Immunology and Allergy
skin and connective tissue diseases
Cell Proliferation
Membrane Potential
Mitochondrial
Gene Expression Profiling
Estrogen Receptor alpha
Cell Biology
Cell cycle
Mitochondria
Gene Expression Regulation
Neoplastic
Tamoxifen
030104 developmental biology
Receptors
Estrogen
Drug Resistance
Neoplasm
Cell culture
030220 oncology & carcinogenesis
Cancer research
Signal transduction
GPER
hormones
hormone substitutes
and hormone antagonists
Signal Transduction
Zdroj: Journal of Leukocyte Biology. 105:983-998
ISSN: 1938-3673
0741-5400
Popis: Estrogens demonstrate biological activity in numerous organ systems, including the immune system, and exert their effects through estrogen receptors (ER) of two types: intracellular ERα and ERβ that activate transcriptional factors and membrane G protein-coupled ER GPER. The latter is capable to mediate fast activation of cytosolic signaling pathways, influencing transcriptional events in response to estrogens. Tamoxifen (TAM), widely used in chemotherapy of ERα-positive breast cancer, is considered as an ERα antagonist and GPER agonist. TAM was shown to possess “off-target” cytotoxicity, not related to ER in various tumor types. The present work was designed to study biological effects of TAM on the glucocorticoid (GC)-resistant cell line Jurkat, derived from acute lymphoblastic leukemia of T lineage (T-ALL). We have shown that T-ALL cell lines, in contrast to healthy T cells, express only GPER, but not ERα or ERβ. TAM compromised mitochondrial function and reduced the viability and proliferation of Jurkat cells. Additionally, TAM induced autophagy in a GPER-dependent manner. Gene expression profiling revealed the up-regulation of autophagy-related gene ATG5. Interestingly, TAM sensitized Jurkat cells to dexamethasone (DEX) treatment, which may be related to its capacity to cause autophagy. We suggest that TAM-based adjuvant therapy may represent a novel strategy in T-ALL patients handling.
Databáze: OpenAIRE
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